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OBJECTIVE: To compare preoperative chlorhexidine- 2.1–3.3; n579) for chlorhexidine-alcohol and 3.6% (95%
alcohol topical antiseptic agent with povidone-iodine in CI 2.7–4.8; n545; P5.09) for the povidone-iodine group.
patients undergoing abdominal hysterectomy for benign Using multivariate logistic regression and adjusting for
indications. differences between populations in patient demographic
METHODS: A retrospective cohort study of patients factors (age and body mass index), medical comorbid-
undergoing abdominal hysterectomy from July 2012 to ities (American Society of Anesthesiologists class and
February 2015 in the Michigan Surgical Quality Collab- diabetes status), perioperative variables (estimated blood
orative was performed. The primary exposure was the loss, surgical time, intraoperative adhesions, and
use of chlorhexidine-alcohol or povidone-iodine. The antibiotic categories), and hospital characteristics (bed
primary outcome was surgical site infection within 30 size and teaching status), we estimate that patients
days. Multivariable logistic regression and propensity receiving chlorhexidine-alcohol had 44% lower odds
score matching analysis were done to estimate the of developing a surgical site infection (adjusted odds
independent association of skin antiseptic choice on ratio 0.56, 95% CI 0.37–0.85, P5.01). Propensity score
the rate of surgical site infection. matching (one to one) yielded 808 patients in the
chlorhexidine-alcohol group and 845 patients in the
RESULTS: Of the total 4,259 abdominal hysterectomies
povidone-iodine group. In the matched groups, the rate
included, chlorhexidine-alcohol was used in 70.5%
of surgical site infection was 1.5% (95% CI 0.8–2.6; n512)
(n53,005) and povidone-iodine in 29.5% (n51,254) of
for the chlorhexidine-alcohol group and 4.7% (95% CI
surgeries. The overall unadjusted rate of any surgical site
3.5–6.4; n540) for the povidone-iodine group (P,.001).
infection was 2.9% (95% CI 2.5–3.5; n5124). The
unadjusted rate of surgical site infection 2.6% (95% CI
CONCLUSION: In abdominal hysterectomy performed
for benign indications, chlorhexidine-alcohol-based skin
From the Departments of Obstetrics & Gynecology and Surgery and the Institute
of Healthcare Policy and Innovation, University of Michigan, Ann Arbor, and the antisepsis is associated with overall lower odds of
Department of Obstetrics and Gynecology, St. John Hospital and Medical Center, surgical site infection compared with povidone-iodine.
Detroit, Michigan. (Obstet Gynecol 2017;130:319–27)
Presented as an oral plenary during the Society of Gynecologic Surgeons’ 42nd DOI: 10.1097/AOG.0000000000002130
annual meeting, April 10–13, 2016, Palm Desert, California.
S
The authors thank Dr. Karen McLean and the Michigan Gynecologic Oncology urgical site infections have been linked to longer
Workgroup for their feedback on this project and Sarah Block for her editorial
assistance. hospital stays, higher readmission rates, and
Each author has indicated that he or she has met the journal’s requirements for
increased health care costs.1–3 Approximately
authorship. 200,000 hysterectomies performed each year in the
Corresponding author: Shitanshu Uppal, MBBS, Department of Obstetrics and United States are done through a laparotomy.4 The
Gynecology, Division of Gynecologic Oncology, University of Michigan, 1500 overall rate of surgical site infection after abdominal
East Medical Center Drive, Ann Arbor, MI 48109; email: uppal@med.umich. hysterectomy has been reported to be approximately
edu
4–6%.5,6 Furthermore, surgical site infections are
Financial Disclosure
The authors did not report any potential conflicts of interest. responsible for one third of the readmissions after
hysterectomy.3 Therefore, reduction in surgical site
© 2017 by The American College of Obstetricians and Gynecologists. Published
by Wolters Kluwer Health, Inc. All rights reserved. infections after abdominal hysterectomy has become
ISSN: 0029-7844/17 one of the Centers for Medicare & Medicaid Services’
VOL. 130, NO. 2, AUGUST 2017 Uppal et al Chlorhexidine-Alcohol Use in Hysterectomy 321
Demographics
Age (y) 47.09610.11 47.5169.82 .648
Race
White or Caucasian 2,590 (97.2) 74 (2.8) .502
Nonwhite 1,545 (96.9) 50 (3.1)
BMI (kg/m2) 31.3768.64 34.6468.64 ,.001
Insurance status
Private 2,796 (97.3) 78 (2.7) .214
Medicare 406 (97.8) 9 (2.2)
Medicaid 653 (95.9) 28 (4.1)
Uninsured 73 (98.6) 1 (1.4)
Missing or other 207 (96.3) 8 (3.7)
Medical comorbidities
ASA class
Less than 3 25 (96.2) 1 (3.9) .040
3 or greater 4,110 (97.1) 123 (2.9)
Functional status
Dependent 3,791 (97.2) 110 (2.8) .776
Independent 344 (96.1) 14 (3.9)
Diabetes present
No 3,039 (97.3) 86 (2.8) .24
Yes 1,096 (96.7) 38 (3.4)
Tobacco use in past year
No 3,039 (97.3) 86 (2.8) .304
Yes 1,096 (96.7) 38 (3.4)
Alcohol use in the past year
No 4,092 (97.1) 122 (2.9)
Yes 43 (95.6) 2 (4.4)
Perioperative variables
Skin antiseptic choice
Chlorhexidine-alcohol 2,926 (97.4) 79 (2.6) .090
Povidone-iodine 1,209 (96.4) 45 (3.6)
Preoperative antibiotic
b-lactam 3,458 (97.3) 97 (2.8) .115
b-lactam alternative 677 (96.2) 27 (3.8)
Intraoperative variables
Estimated blood loss (mL) 317.946339.66 349.606369.93 .308
Surgical time (min) 124.95659.86 137.91675.67 .019
Intraoperative adhesions
None 2,935 (97.5) 76 (2.5) .002
Minor 494 (97.6) 12 (2.4)
Major 706 (95.2) 36 (4.8)
Bowel surgery
No 4,090 (97.2) 118 (2.8) ,.001
Yes 45 (88.2) 6 (11.8)
Hospital characteristics
Bed size
Less than 300 beds 1,224 (96.9) 39 (3.1) .387
300–499 beds 1,848 (97.1) 55 (2.9)
Greater than 500 beds 954 (97.6) 24 (2.4)
Unknown 109 (94.8) 6 (5.2)
Teaching status
Community hospital 1,602 (97.3) 44 (2.7) .284
Academic hospital 2,424 (97) 74 (3)
Unknown 109 (94.8) 6 (5.2)
BMI, body mass index; ASA, American Society of Anesthesiologists.
Data are mean6SD or n (%) unless otherwise specified.
Demographics
Age (y) 46.7469.45 47.96611.46 ,.001 47.1469.83 46.85610.38 .554
Nonwhite race 1,267 (42.2) 328 (26.2) ,.001 258 (32) 279 (33) .637
BMI (kg/m2) 31.8168.08 30.6669.87 ,.001 30.9767.56 30.85610.90 .800
Insurance status
Medicare 259 (8.6) 156 (12.44) .003 76 (9) 76 (9) .888
Medicaid 483 (16.1) 198 (15.8) 131 (16) 134 (16)
Private 2,050 (68.2) 824 (65.7) 548 (68) 574 (68)
Uninsured 52 (1.7) 22 (1.8) 11 (1) 17 (2)
Missing or other 161 (5.4) 54 (4.3) 42 (5) 44 (5)
Medical comorbidities
ASA class 3 or greater 742 (24.7) 238 (19.0) ,.001 169 (21) 161 (19) .344
Functional status dependent 25 (0.8) 1 (0.1) .004 3 (0) 1 (0) .295
Diabetes present 251 (8.4) 107 (8.5) .847 63 (8) 70 (8) .716
Tobacco use in past year 780 (26.0) 354 (28.2) .126 218 (27) 228 (27) .999
Alcohol use in the past year 33 (1.1) 12 (1.0) .681 10 (1) 11 (1) .907
Perioperative variables
Preoperative antibiotics
b-lactam alternatives 522 (17.4) 182 (14.5) 103 (13) 93 (11) .548
Intraoperative variables
Estimated blood loss (mL) 348.726360.96 247.316273.02 ,.001 285.256299.78 272.456306.73 .391
Surgical time (min) 131.03661.19 111.65656.21 ,.001 118.14651.30 116.84660.81 .640
Intraoperative adhesions
None 2,038 (67.8) 973 (77.6) ,.001 285.25 (299.78) 272.45 (306.73) .859
Minor 382 (12.7) 124 (9.9) 285.25 (299.78) 272.45 (306.73)
Major 585 (19.5) 157 (12.5) 285.25 (299.78) 272.45 (306.73)
Bowel surgery
Yes 46 (1.5) 5 (0.4) .002 7 (1) 5 (1) .511
Hospital characteristics
Bed size
Less than 300 beds 858 (28.6) 405 (32.3) ,.001 248 (31) 283 (33) .464
300–499 beds 1,314 (43.7) 589 (47) 379 (47) 384 (45)
Greater than 500 beds 757 (25.2) 221 (17.6) 181 (22) 178 (21)
Unknown 76 (2.5) 6 (3.1) 0 0
Teaching status
Community hospital 921 (30.7) 725 (57.8) ,.001 426 (53) 429 (51) .427
Academic hospital 2,008 (66.8) 490 (39.2) 382 (47) 416 (49)
Unknown 76 (2.5) 39 (3.1) 0 0
BMI, body mass index; ASA, American Society of Anesthesiologists.
Data are mean6SD or n (%) unless otherwise specified.
similar with none of the factors significantly different povidone-iodine use had higher rates of surgical site
between the two groups (Table 2). The rate of surgi- infection.
cal site infection in the matched cohort was 1.5%
(95% CI 0.8–2.6; n512) for the chlorhexidine- DISCUSSION
alcohol group and 4.7% (95% CI 3.5–6.4; n540; In patients undergoing abdominal hysterectomy in
propensity matched cohort OR 0.31, 95% CI 0.17– a statewide collaborative, preoperative skin prepara-
5.6, P,.001; Table 3). tion with chlorhexidine-alcohol is associated with
Figure 2 highlights the increase in surgical site lower odds of developing surgical site infection
infection as a function of proportion of hysterectomies compared with povidone-iodine (adjusted OR 0.56).
using povidone-iodine skin preparation at each This finding is important for several reasons. Abdom-
hospital site. Hospitals with a higher rate of inal hysterectomy remains common in the United
VOL. 130, NO. 2, AUGUST 2017 Uppal et al Chlorhexidine-Alcohol Use in Hysterectomy 323
Surgical site
infection
(any)
No 2,926 (97.4) 1,209 (96.4) 0.09 796 (98.5) 805 (95.3) ,.001
Yes 79 (2.6) 45 (3.6) 12 (1.5) 40 (4.7)
Data are n (%) unless otherwise specified.
States with 200,000 open abdominal hysterectomies after hysterectomy (compared with other procedures
performed per year. Therefore, evidence-based inter- like bowel surgery), these results needed further inves-
ventions to reduce surgical site infections are urgently tigation in patients undergoing hysterectomy.
needed. Second, surgical site infections after abdom- Similarly, a comprehensive systematic review found
inal hysterectomy will be a metric included in the an overall risk reduction of 32% with the use of
Hospital Acquired Condition Reduction Program chlorhexidine-alcohol compared with povidone-
score, which will affect hospital reimbursements.20 iodine in clean-contaminated surgery.23
Third, surgical site infections are the single most sig- The mechanism of action and the superiority of
nificant cause for readmissions after hysterectomy.3 chlorhexidine-alcohol seem to be related to its
Finally, surgical site infections have been shown to persistent activity with rapid onset of action related
be associated with a significant increase in morbidity to drying of alcohol and the ability of chlorhexidine
and mortality after surgery as well as a negatively to remain active even when the field is soiled with
effect on patient quality of life of patients.21 Although blood or serum.24 However, it is unclear whether the
major perioperative guidelines specify the choice of superiority of chlorhexidine-alcohol is the result of
antibiotics to prevent infections, to our knowledge, the alcohol base or the chlorhexidine component
there are no current established national guidelines itself. In cesarean deliveries, Tuuli et al25 reported
that indicate the choice of preoperative topical skin that the use of chlorhexidine-alcohol for preopera-
antisepsis before abdominal hysterectomy. Our find- tive skin antisepsis resulted in a significantly lower
ings, along with the previous randomized controlled risk of surgical site infections when compared with
trials in the field of general surgery, provide a basis for iodine in alcohol, indicating that chlorhexidine
recommending chlorhexidine-alcohol for abdominal gluconate may help decreases the rate of surgical site
hysterectomy.12 infection. Further studies comparing alcohol-based
Our results are consistent with previous studies preparations are needed to answer this question,
comparing povidone-iodine with chlorhexidine- albeit a randomized study may not be feasible as
alcohol. Levin et al22 reported on a study comparing a result of the necessity of a relatively large sample
chlorhexidine-alcohol with povidone-iodine in gyne- size.
cologic surgeries. Overall reduction in surgical site The alcohol-based skin preparations have their
infections with the implementation of chlorhexidine- limitations. Before evaporation, a significant fire risk
alcohol (from 14.6% to 4.5%) was noted in this study. exists and significant injuries to the patient and staff
Although the baseline rates of surgical site infections have been reported.26,27 In addition, these agents
were much higher than previously reported rates in cannot be used on mucosal surfaces. Therefore, aque-
the United States, this study supported the use of ous preparations have a role in vaginal hysterectomy
chlorhexidine-alcohol instead of povidone-iodine. as well as in vaginal preparation during abdominal
Darouiche et al12 reported the results of their random- hysterectomy. Although the isopropyl alcohol and
ized controlled trial and concluded that chlorhexidine gluconate pose a very small risk of
chlorhexidine-alcohol was superior to povidone- combustion at temperatures provided by the electro-
iodine in preventing surgical site infections (rate of surgical devices, the overall qualitative benefits from
16% compared with 9.5%, P5.004, respectively) in a reduction of surgical site infections in the
clean-contaminated surgeries. However, their study chlorhexidine-alcohol group make this agent a supe-
included only 40 gynecologic patients in each arm; rior choice. Strategies to ensure adequate waiting time
given the overall low rate of surgical site infection after skin preparation during timeout to prevent
Demographics
Age (per year) 1.004 1.015 0.987–1.044 .29 X X X
BMI (per 1 kg/m2) 1.02 1.017 0.999–1.036 .06 1.02 1.002–1.045 .04
Insurance status
Private Ref Ref Ref Ref Ref Ref Ref
Medicare 0.569 0.227–1.425 .23 0.72 0.31–1.64 .43
Medicaid 1.467 0.946–2.275 .09 1.47 0.97–2.2 .07
Uninsured 0.546 0.085–3.51 .52 0.55 0.08–3.7 .54
Missing or other 1.398 0.769–2.542 .27 1.4 0.79–2.47 .24
Medical comorbidities
ASA class
Less than 3 Ref Ref Ref Ref X X X
3 or greater 1.5 1.243 0.86–1.797 .25 X X X
Functional status
Dependent NI NI NI NI X X X
Independent NI NI NI X X X
Diabetes status
No Ref Ref Ref Ref X X X
Yes 1.4 0.941 0.489–1.809 .86 X X X
Tobacco use in past year
No NI NI NI NI X X X
Yes NI NI NI NI X X X
Alcohol use in past year
No NI NI NI NI X X X
Yes NI NI NI NI X X X
Perioperative variables
Skin antiseptic choice
Povidone-iodine Ref Ref Ref Ref Ref Ref Ref
Chlorhexidine-alcohol 0.73 0.557 0.37–0.839 .01 0.65 0.45–0.93 .02
Preoperative antibiotics
b-lactam Ref Ref Ref Ref Ref Ref Ref
b-lactam alternative 1.81 1.777 1.144–2.761 .01 1.77 1.16–2.7 .007
Intraoperative variables
Estimated blood loss (per mL) 1 0.999–1.001 .94 X X X
Surgical time (per min) 1.001 0.998–1.005 .48 X X X
Intraoperative adhesions
None Ref Ref Ref Ref Ref Ref Ref
Minor 0.923 0.512–1.663 .79 0.84 0.45–1.56 .59
Major 1.942 1.274–2.959 ,.001 1.83 1.24–2.7 .002
Bowel surgery
No Ref Ref Ref Ref Ref Ref Ref
Yes 4.031 1.414–11.493 .01 4.76 1.7–13.4 .003
Hospital characteristics
Teaching status
Community hospital Ref Ref Ref Ref X X X
Academic hospital 1.11 1.343 0.766–2.353 .3 X X X
Bed size
Less than 300 beds Ref Ref Ref Ref X X X
300–499 beds 0.93 0.822 0.482–1.403 .47 X X X
Greater than 500 beds 0.79 0.656 0.335–1.283 .22 X X X
OR, odds ratio; BMI, body mass index; Ref, referent; ASA, American Society of Anesthesiologists; NI, variable not included in model 1.
X indicates the variable was removed in the backward stepwise regression (cutoff for removal was P..2).
surgical fires are recommended.28,29 Allergies to chlorhexidine-alcohol allergy remain unknown, one
chlorhexidine-alcohol have been reported in the study estimated that skin patch testing revealed
literature. Although the precise estimates of positive reactions in 2% of the patients tested. Further
VOL. 130, NO. 2, AUGUST 2017 Uppal et al Chlorhexidine-Alcohol Use in Hysterectomy 325
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